The epidemiological and economic burden of diabetes in Ghana: A scoping review to inform health technology assessment

Diabetes remains one of the four major causes of morbidity and mortality globally among non-communicable diseases (NCDs. It is predicted to increase in sub–Saharan Africa by over 50% by 2045. The aim of this study is to identify, map and estimate the burden of diabetes in Ghana, which is essential for optimising NCD country policy and understanding existing knowledge gaps to guide future research in this area. We followed the Arksey and O’Malley framework for scoping reviews. We searched electronic databases including Medline, Embase, Web of Science, Scopus, Cochrane and African Index Medicus following a systematic search strategy. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews was followed when reporting the results. A total of 36 studies were found to fulfil the inclusion criteria. The reported prevalence of diabetes at national level in Ghana ranged between 2.80%– 3.95%. At the regional level, the Western region reported the highest prevalence of diabetes: 39.80%, followed by Ashanti region (25.20%) and Central region at 24.60%. The prevalence of diabetes was generally higher in women in comparison to men. Urban areas were found to have a higher prevalence of diabetes than rural areas. The mean annual financial cost of managing one diabetic case at the outpatient clinic was estimated at GHS 540.35 (2021 US $194.09). There was a paucity of evidence on the overall economic burden and the regional prevalence burden. Ghana is faced with a considerable burden of diabetes which varies by region and setting (urban/rural). There is an urgent need for effective and efficient interventions to prevent the anticipated elevation in burden of disease through the utilisation of existing evidence and proven priority-setting tools like Health Technology Assessment (HTA).


Introduction
Diabetes is one of the top four leading causes of non-communicable diseases (NCDs) related mortality globally [1].Approximately 537 million people between the ages of 20-79 years are living with diabetes globally of which over 75% live in low-and middle-income countries (LMICs).Of those living with diabetes nearly half are unaware of their diagnosis [2].Diabetes exerts tremendous pressure on the resources available for health; treatment and management of diabetes account for over 10% of the total health expenditure among adults globally [3].The prevalence of diabetes is expected to increase globally to 783 million by 2045 [2].
As of 2021, there were approximately 24 million people with diabetes in sub-Saharan Africa (SSA) and the number is projected to increase by 134% by 2045.[3].The prevalence of diabetes in the region stands at approximately 4.5% among those aged between 20-79 years.In 2021 alone, over 306,000 people under 60-years of age died due to diabetes in SSA [3].It is estimated that the average annual direct cost on healthcare per person with diabetes in SSA is approximately USD 547 as of 2021.
Most cases of diabetes can be classified into two types: Type 1 diabetes (T1D) is most common in children and results from the destruction of insulin-producing beta cells, mostly by autoimmune mechanisms [4].T2D is linked to physical inactivity and an unhealthy diet, and accounts for approximately 90% of all diabetes cases globally [5].
While regional estimates are available to support policy making, there is a need to understand the country-specific disease burdens (national and sub-national) to inform target policy at a local level that yields effective and economically efficient impact.Unfortunately, existing estimates of country-specific diabetes burden are sparse in low and lower middle-income settings, especially in SSA.This makes it difficult to identity and implement appropriate targeted interventions that are feasible and affordable by a given country considering the existing financial constraints of the health budgets.Countries in SSA are starting to adopt health technology assessment (HTA) as a decision-making aid to identify and implement appropriate interventions while maximizing value for money.Fig 1 illustrates the main steps involved in HTA processes as adapted from Siegfried et al. [6].
HTA can be defined as a multidisciplinary process that uses explicit methods, often involving cost-effectiveness analysis, to determine the value of a health technology at different points in its lifecycle [7].An important input into the conduct of HTA includes having credible estimates of disease burden, which will be important in informing key parameters in any costeffectiveness model [8].
HTA can be used to identify diabetes interventions and negotiate prices of diabetes drugs and related medical equipment [9,10].The Ghana Ministry of Health has indicated an interest in using HTA to inform decision making in diabetes management and prevention.This is in line with the country's commitment to implement evidence informed priority setting [11,12].Such an approach requires comprehensive up-to date information about the current epidemiological and economic burden of diabetes in the country [9], which is currently unavailable [13].A systematic review on diabetes by Asamoah-Boaheng et al. [14] had been carried out but focused on T2D, did not include the prevalence of diabetes comorbidities nor the economic burden.In addition, updated evidence on diabetes prevalence was necessary.
To address this need, our study aims to undertake a scoping review of the peer-reviewed literature to identify, map and estimate the burden of diabetes in Ghana, in terms of epidemiological distribution, health outcomes and economic consequences.It is anticipated this work will support optimising current NCD country policy, especially in relation to priority setting, as well inform the parameterisation of model-based analyses and highlight existing knowledge gaps to guide future research in this area.

Ethics statement
The study utilised secondary data/literature that is publicly available and did not use any personal or private data.

Study design
We followed the Arksey and O'Malley framework for scoping reviews [15].The framework consists of five stages which were followed: (i) identifying the research question; (ii) identifying relevant studies; (iii) selecting appropriate studies; (iv) charting and collating the data, and (v) summarising and reporting the results.The detailed search protocol is available in S1 Text.A study protocol is available although not registered.We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) in reporting the results [16].We examined the following aspects of burden: (1) epidemiological distribution (incidence, prevalence, demographic distribution), (2) impact on health outcomes (comorbidity or complications, health effects in disability adjusted life years (DALYs), quality adjusted life years (QALYs), mortality among others), and (3) economic consequences (cost of care, loss of productivity, or out of pocket expenditure).

Eligibility criteria and study selection
A study was considered eligible for inclusion if it was published in a peer-reviewed journal and reported burden of disease in Ghana.We defined burden in this regard as any article reporting on incidence, prevalence and or economic consequences of diabetes.To ensure relevance, we only included studies published after 2009.All study designs were considered for inclusion without restrictions.The population in this study are people with any form of diabetes.We did not have any restrictions on age or sex.Literature reporting only the qualitative experience of diabetic patients, and those assessing the relationship between socioeconomic status (SES), gender, and diabetes as a health outcome were excluded.Studies published in languages other than English were also excluded.

Information sources
We searched the following electronic databases: Medline, Embase, Web of Science, Scopus, Cochrane and African Index Medicus.The databases were searched on 4 th April 2021 following a systematic search strategy and a second search was done on 11 th April 2023 to find all new articles that were published since the previous search.

Search strategy
We used two broad key terms ('Ghana' and 'diabetes') as well as similar derivatives, to identify the literature on the burden of disease.Search strings were tailored to the different databases (S1 Text).

Selection process
The retrieved articles from the search were listed and uploaded to Covidence software [17] which was used to identify and remove duplicates, carry out the screening process and full-text review.A standard process of screening articles by title and abstract, followed by full-text reading was followed to assess eligibility to be included in this study.These steps were conducted by two independent researchers (MG & JK).Any discrepancies in the assessment decision were discussed and resolved by reaching a consensus between the two researchers.

Data charting
A data extraction sheet was used to extract relevant information from included studies to allow us to map and highlight the main results and categorize findings in relation to the research question.We developed the data extraction sheet based on the aim of the study and we pretested the data extraction sheet on five articles prior to starting the data extraction.Changes were made to the sheet following the pilot.Information extracted using the data extraction sheet included: author name, publication year, form of diabetes burden being reported (such as prevalence, incidence, economic, etc), study design, target population, geographical region, setting (urban or rural), and main findings.
Our charting approach allowed us to interpret data from included studies according to the forms of diabetes burden which we henceforth refer to as themes.The extracted data was grouped under three themes (epidemiological, health outcomes, economic).We used pie charts, frequency tables, bar graphs and basic descriptive analytical techniques to summarise and report the scoping review findings.

Synthesis of results
We organised extracted data quantitatively following the themes.We produced tables and charts in relation to the following: the distribution of studies geographically and per type of burden, target groups; the research methods adopted, and health outcome measures used.

Results
The electronic database search yielded 1103 records after deduplication.

Study characteristics
A total of 36 studies fulfilled the inclusion criteria.Table 1 shows the characteristics of the included studies.All studies were observational studies with a majority having a cross-sectional design (n = 30); there were four longitudinal studies [18][19][20][21] and two case control studies [22,23].The longitudinal studies were based on either panel data or cohort study data.

Publication trend
The number of publications by year (Fig 3) broadly shows an increasing trend between 2009 and 2019 and a dip after 2019.Most articles were published in 2019 (n = 7) before a decline in 2020.

Forms of the burden of diabetes (themes) in Ghana
Our charting analysis mapped the studies across three main themes: epidemiological, health outcomes, and economic.The epidemiological theme included prevalence of diabetes (n = 16) and incidence (n = 2).The health outcomes theme (n = 17) was comprised of studies reporting on complications (n = 6), comorbidities (n = 10) and mortality (n = 1).Finally, the economic theme (n = 1) included costs of diabetes services.Some studies reported both the prevalence of diabetes and comorbidities (n = 1).Frequency of theme by region.The Ashanti and Greater Accra regions were the most frequently targeted regions across all studies, with reported studies covering all the three themes.We found data on both prevalence and outcomes in the Volta and Central regions.The Western region had only prevalence data reported while Brong-Ahafo and Northern regions had studies that reported on health outcomes only.No data was found for the remaining regions.Five studies were conducted using a nationally representative sample.Fig 5 shows the frequency of themes by region from all included studies (including single and multi-region studies).

1) Epidemiological burden
The reported prevalence of diabetes at national level in Ghana ranged between 2.80% [25, 26]-3.95%[24].At sub-national levels, the Western region reported the highest prevalence of diabetes: 39.80% among those 18 years and older [40].The second highest prevalence of diabetes (25.20%) was reported in Ashanti region [50] followed by 24.60% in the Central region [40].
In the national studies, the prevalence of diabetes was generally higher in women in comparison to men [24,26,38].Regionally, the prevalence of diabetes was also notably higher in females compared to males, with the exception of the Ashanti region [28,32,50,51].Urban areas had a higher prevalence than rural areas [24-26, 41, 42].
Prevalence studies only covered five of the ten administrative regions: Ashanti (n = 6), Volta (n = 3), Central (n = 2), Greater Accra (n = 2), and Western (n = 1) regions.There were four national-level studies.The majority of prevalence studies were focused on adults aged 18 years old and above (n = 7), followed by adults 50 years and above (n = 4).Table 2 shows the summary of studies that reported the prevalence of diabetes in Ghana.

2) Common complications and comorbidity
Seven complications and/or comorbidities were identified in this review (Fig 6).Studies on complications and comorbidities were only found for six of the ten administrative regions: Ashanti (n = 9), Northern (n = 2), Greater Accra (n = 2), Volta (n = 2), Brong-Ahafo (n = 1) and Central (n = 1).In addition, a multi-region (sub-national) study combining populations from Greater Accra, Ashanti, and Northern regions (n = 1) was identified along with a study that did not specify location (n = 1).No study was conducted at the national level for complications and comorbidities of diabetes.
Six studies assessed the prevalence of metabolic syndrome in diabetic patients in Ghana in the regions of Ashanti, Northern, Volta and Brong-Ahafo.The highest prevalence rate of metabolic syndrome was reported in the Ashanti region, with prevalence ranging between 42% [52] and 90% [45].This was followed by Brong-Ahafo with 68.6% [37], the Volta region with 43.8% [29], and Northern region with 24% [36].The prevalence of hypertension among diabetic patients was assessed in three studies that included populations of Ashanti, Northern, and Greater Accra regions.The highest prevalence of hypertension as a complication/ comorbidity of diabetes was reported in the Greater Accra region (36.60%).This was followed by the Northern region (21%), and the Ashanti region (1.61%).Diabetic foot disorders and lower extremity amputation were assessed in four studies.Two longitudinal studies were conducted in Komfo Anokye Teaching Hospital in the Ashanti region reporting a mean incidence of foot disorders and average incidence rate of diabetes related amputations of 8.39% (5.27% males and 3.12% females) [21] and 2.4 (95% CI:1.84-5.61)per 1000 follow-up years [20] respectively among diabetes patients.The third study was a cross-sectional study that randomly selected patients from the outpatient diabetes clinics of three tertiary hospitals from Greater Accra, Ashanti, and Northern regions and reported a prevalence of 11% for diabetic foot ulcers and 3% for lower extremity amputations.The fourth study was also cross sectional in Volta region focusing on diabetic foot ulcers [30].
One study assessed the prevalence of depression among diabetic patients at the National Diabetes Management and Research Centre, Korle Bu Teaching Hospital in Greater Accra region [33].The study reported that 31% of diabetic patients suffered from depression in 2018.Finally, a case-control study reported that 84.8% of patients with diabetes had haemoglobin concentrations that were significantly lower than the general population.Table 3 provides a summary of findings stratified by complication type and geographic region in Ghana.

Context
Sample size

Diagnostic criteria Main results
(Continued )

3) Economic burden
Only one study reported on the economic burden of diabetes, assessing the financial cost of diabetes management (from a provider perspective) in cocoa clinics in Greater Accra, Ashanti, and Eastern regions [27].Bottom-up micro costing was used to estimate the costs.The mean annual financial cost of managing one diabetic case at the outpatient clinics was estimated at GHS 540.3 (2021 US $194.09).The costs were broken down between service costs (22%) and direct medical costs (78%).Drug costs accounted for 71% of the direct medical costs.The cost of hospitalization per patient-day at clinics was estimated at GHS 32.78 (2021 US$ 11.78).The total annual financial cost of diabetes management accounted for 8% of the total annual expenditure of the clinics.

Discussion
This scoping review reveals that there is paucity of literature on the burden of diabetes in Ghana.We divided the burden into three forms (themes): epidemiological burden (prevalence and incidence of diabetes); health outcomes (mortality, diabetes complications and comorbidity); and economic burden (cost of illness to the patients and health system).Most of the existing Ghana centred literature focuses on the prevalence of diabetes, including its complications and comorbidities.There is sparse data on the economic burden of the disease in Ghana.This review did not find any study that used generic health outcome measures such as DALYs or QALYs to estimate the diabetes burden.The existing literature is skewed towards a few particularly Ashanti, leaving some geographical regions of Ghana without any reporting (including, for example, Upper East, and Upper West regions).Out of the identified studies, 36 studies focused on the prevalence of diabetes and associated complications; only one study reported economic-related findings, indicating a need for more costing studies, important also to support the development of economic evaluations.All diabetes studies were either on T2D or referred to diabetes generally without specifying the type.No studies explicitly targeting T1D were found.Our findings suggest important gaps in the Ghanaian scientific literature, and the need for further research to characterise the burden of diabetes in the country.
The national prevalence of diabetes in Ghana was reported in the studies to be between 2.80% and 3.95% [24][25][26] which is less than the pooled value of 6.5% by Asamoah-Boaheng et al. [14].This is because Asamoah-Boaheng pooled both regional and national findings.Furthermore, Asamoah-Boaheng et al. [14] considered an earlier period (2000-2009) which we didn't include in our study.Our reported national prevalence of diabetes (2.8% to 3.95%) is below the sub-Saharan Africa regional average of 4.5% [3].However, studies that reported on prevalence sub-nationally provided substantially higher estimates; for example in Western, Ashanti, and Central regions, diabetes prevalence was reported to be 39.8% [40], 25.2% [50] 24.6% [40] respectively.Despite Ghana having seemingly lower levels of prevalence of diabetes at a national level in comparison to the SSA average, it should be noted that the studies reporting high prevalence undertook screening for diabetes [40,50].This could indicate that the prevalence of undiagnosed diabetes may be a lot higher in some regions than feared, although further research is needed to confirm those findings.Nevertheless, there remains an urgent need to put in place interventions to address these regional differences, and stem any further anticipated rise in disease burden [3].The within-country regional variations call for a more targeted approach when implementing diabetes interventions.
Diabetes in Ghana was found to be more prevalent among women compared to men [24][25][26]32].This is in line with the recently reported prevalence in SSA by International Diabetes Federation [3] and other studies [54,55].Systematic reviews have found that women were more likely to have diabetes [odds ratio1.65 (95% CI 1.43, 1.91)], and less likely to have glycaemic control than men.It has been argued that relative differences in physical activity between men and women may be a factor [54].There was an urban-rural divide in the prevalence of diabetes in Ghana where urban areas were reported to have a higher prevalence compared to the rural areas [24-26, 41, 42].This finding is consistent with other studies done in India (prevalence of 15.0% and 19.0% in rural and urban areas respectively in the year 2015-2019) [56], and Myanmar (prevalence of 7.1% and 12.1% in rural and urban areas respectively in year 2013/2014) [57].This has been attributed to differences in dietary habits and levels of physical activity between urban and rural areas.
Hypertension and metabolic syndrome were among the most prevalent comorbidities of diabetic patients in Ghana.Hypertension prevalence was highest in the Greater Accra region (36.60% of diabetic patients) [34].Metabolic syndrome is a cluster of conditions that include combinations of hypertension, central obesity, insulin resistance, or atherogenic dyslipidaemia [58].The two main risk factors of metabolic syndrome are the increase in consumption of high-calorie, low-fibre fast food and a decrease in physical activity which may be linked to mechanized transportation and a sedentary form of leisure time activities.These are the same established behavioural risk factors for diabetes and obesity that are typically predominant in urban areas.Without treatment, diabetes, high blood pressure, and obesity can damage blood vessels, leading to micro and macrovascular complications, which can occur concurrently.The highest prevalence of metabolic syndrome was reported in the Ashanti region where it was reported to range from 59 to 90% among diabetic patients [44,45].
Our results also align well with the Institute of Health Metrics and Evaluation (IHME) assessment of the trend of disease burden in Ghana.Notably, in the year 2000, diabetes was not within the top 10 disease groups in terms of burden of disease.By 2019 diabetes had moved up to eighth position and was linked to more than 2,157 DALYs per 100,000 people.Cardiovascular diseases, which are often complications of diabetes and metabolic syndrome, were ranked first in 2019, causing an estimated 6,216 DALYs per 100,000 population [59].This evidence points to the rapid rise of diabetes, cardiovascular diseases and other NCDs, linked with common genetic, metabolic, and behavioural risk factors.The ranking also suggests that there is a gradual receding of communicable diseases in the last 2 decades compared to NCDs.Combined, diabetes and cardiovascular diseases is linked to more than 8,300 DALYs per 100,000 people in Ghana, representing a significant proportion (12.6%) of the total disease burden in the country [59].
Literature on the economic burden of diabetes in Ghana is very limited with only one study reporting on the burden.This finding is in line with the study by Hollingworth et al. (2020) that looked at available localised information to support HTA in Ghana noting that there were few accessible data sources for costs and resource utilisation generally [8].Relatedly, we found a falling off in the number of studies published after 2019, although that may reflect the impact of the COVID-19 pandemic on research and publication choices within the country and globally.

Policy implications
Our review provides some evidence of the situation in Ghana, and associated information gaps, consistent with studies focused on other African countries [60].We find that Ghana is faced with a rising prevalence of diabetes and cardiovascular disorders with potentially important regional differences in disease burden.To address this challenge, there is a need to understand the contextual factors driving the rise and the likely causes behind the existing regional variations in the reported burden.
Unlike communicable diseases, NCDs are usually chronic in nature and exhibit a progressive disease course.A person may develop more than one NCD at a time, fuelling disease progression even further [61,62].NCDs constitute a long-term burden not only to the patient and carers, but also to the healthcare system and the economy.Currently, NCDs do not attract as much development assistance funds as communicable diseases such as HIV, tuberculosis and malaria, and Ghana which is currently classed as a middle-income country is no longer eligible for some development assistance grants.Therefore, there is a need for Ghana, as well as countries, to ensure that available domestic resources for health can be used as efficiently as possible to address this growing burden.Typically, this involves operationalising and institutionalising proven priority-setting processes.
HTA can be applied to both treatments for NCDs, such as insulin analogues for the management of diabetes, and also to interventions that seek to reduce disease prevalence and incidence in the first place.On the latter this could include identifying cost-effective interventions to tackle the common NCD risk factors shared by diabetes and other comorbidities such as cardiovascular diseases, obesity, or metabolic syndrome to reduce the burden of diabetes in the country.This may require stronger prevention approaches [63] targeting high risk individuals or whole populations, which aim to increase physical activity and promote a healthy diet while also monitoring obesity levels.This would be especially important in urban communities in Ghana where the burden appears higher than the national average.
Institutionalising HTA for localised decision making requires that relevant data sources are available, and that may mean developing a strategy to address key informational gaps as part of building any HTA system.There was a scarcity of evidence on the economic burden of diabetes in Ghana, and there were no estimates available of the burden of disease for a number of regions.A key issue is the lack of diabetes incidence data: as previously reported [8], the Ghana Health and Demographic Surveillance Systems (GHDSS) could potentially be a valuable source of such information, and the Ministry of Health and other stakeholders could consider enhancing their operation in this space, for diabetes as well as other NCDs.It may also mean better leveraging already existing data sources, such as from the National Health Insurance Scheme [8].

Limitations
The scoping review did not include an appraisal of the quality of included studies.According to Arksey and O'Malley's (2005) framework, the study quality is not assessed during scoping reviews, but rather in systematic reviews that aim to address specific questions relating to feasibility, appropriateness, meaningfulness or effectiveness of a certain treatment or practice.The exploratory nature of our study about the burden of diabetes made the scoping review methodology suitable.
The included studies used different diagnostic criteria for diabetes including WHI criteria, American Diabetes Association and self-reporting.Self-reported diabetes can be misleading because some of the people involved in the studies may not have received a diagnosis and thus report as not having the diabetes.This may have underestimated the prevalence of diabetes in the country or region.
This study has used an older geographical classification system for the administrative regions in Ghana.The sub-national regions of Ghana constitute the first level of subnational government administration within the country.From 1987, Ghana had ten officially established regional boundaries.In 2018, a referendum on the creation of six new regions was held and the overall number were later increased to 16.We used the older system of 10 regions based on the available literature which mostly reported within that classification system.However, we expect that there would be no substantial differences had the newer system been applied, since all new regional divisions stem from the partitioning of regions where no studies were found (e.g, Brong Ahafo and Northern regions).

Conclusion
Ghana is faced with a considerable burden of diabetes which varies by geographical region and setting (rural/urban).It is urgent to tackle the growing challenge to mitigate the likely enormous burden and cost of the disease.Despite the existing regional variation of the burden of diabetes, there is a paucity of literature in some regions (for example Eastern, Western, Upper East, Upper West, and Brong Ahafo).There is therefore a need for further research to understand the burden (epidemiological, health outcomes and economic) of diabetes in these regions in order to inform the NCD prevention and management policies in the country.